title: Inhibitory effects of herbal alkaloids on the tumor necrosis factor-α and nitric oxide production in lipopolysaccharide-stimulated RAW264 macrophages.
abstract: It is beneficial to treat chronic inflammatory condition in patients through diets that inhibit the production of proinflammatory cytokines and mediators such as tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Since less attention has been paid to alkaloids in the diets than to polyphenols in this regard, we aimed at investigating anti-inflammatory activity of herb-derived alkaloids through suppression of TNF-α and NO production in lipopolysaccharide (LPS)-stimulated mouse RAW264 and/or human THP-1 cells. A harmala alkaloid, harmine, an opium alkaloid, papaverine, and Lycoris alkaloids, lycorine and lycoricidinol, showed TNF-α suppressive activities stronger than or comparable to that of a reference polyphenol, butein, in RAW264 cells (IC(50)=4, 10, 2.1, 0.02, and 8 µM, respectively). Other alkaloids showed no or marginal to moderate inhibitory activities. Similar tendency of inhibition was found for NO production in RAW264 cells and TNF-α production in THP-1 cells. In addition, harmine was found to suppress interleukin-6 (IL-6) production in RAW264 cells. The above four inhibitory alkaloids had essentially no antioxidative property in the superoxide anion scavenging assay. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that harmine caused neither prevention of nuclear factor-κB (NF-κB) translocation into the nucleus nor inhibition of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, while that the LPS-induced transcription of TNF-α and inducible NO synthase was dose-dependently attenuated by harmine. This result suggests that the molecular mechanism of harmine action is different from those of many other anti-inflammatory phytochemicals. In conclusion, some herbal alkaloids like harmine, in spite of lacking antioxidative property, have potential as anti-inflammatory agents that strongly suppress TNF-α and NO production by a unique mechanism.
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan. y.yamazaki@aist.go.jp
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawano
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases